Chance in agrammatic sentence comprehension: What does it really mean? Evidence from eye movements of German agrammatic aphasic patients

Background: In addition to the canonical subject-verb-object (SVO) word order, German also allows for non-canonical order (OVS), and the case-marking system supports thematic role interpretation. Previous eye-tracking studies (Kamide et al., 2003 Kamide, Y., Scheepers, C. and Altmann, G. M. 2003. Integration of syntactic and semantic information in predictive processing: Cross-linguistic evidence from German and English. Journal of Psycholinguistics Research, 32: 37–54. doi: 10.1023/A:1021933015362 [Google Scholar]; Knoeferle, 2007 Knoeferle, P. 2007. “Comparing the time-course of processing initially ambiguous and unambiguous German SVO/OVS sentences in depicted events”. In Eye movement research. A window on mind and brain, Edited by: van Gompel, R., Fischer, M., Murray, W. and Hill, R. 517–531. Oxford, , UK/Amsterdam: Elsevier.  [Google Scholar]) have shown that unambiguous case information in non-canonical sentences is processed incrementally. For individuals with agrammatic aphasia, comprehension of non-canonical sentences is at chance level (Burchert et al., 2003 Burchert, F., De Bleser, R. and Sonntag, K. 2003. Does morphology make the difference? Agrammatic sentence comprehension in German. Brain and Language, 87: 323–342. doi: 10.1016/S0093-934X(03)00132-9[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). The trace deletion hypothesis (Grodzinsky 1995 Grodzinsky, Y. 1995. A restrictive theory of agrammatic comprehension. Brain and Language, 50: 27–51. doi: 10.1006/brln.1995.1039[Crossref], [PubMed], [Web of Science ®] , [Google Scholar], 2000 Grodzinsky, Y. 2000. The neurology of syntax: Language use without Broca's area. Behavioral and Brain Sciences, 23: 1–71. doi: 10.1017/S0140525X00002399[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) claims that this is due to structural impairments in syntactic representations, which force the individual with aphasia (IWA) to apply a guessing strategy. However, recent studies investigating online sentence processing in aphasia (Caplan et al., 2007 Caplan, D., Waters, G., DeDe, G., Michaud, J. and Reddy, A. 2007. A study of syntactic processing in aphasia I: Behavioral (psycholinguistic) aspects. Brain and Language, 101: 103–150. doi: 10.1016/j.bandl.2006.06.225[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]; Dickey et al., 2007 Dickey, M. W., Choy, J. J. and Thompson, C. K. 2007. Real-time comprehension of Wh-movement in aphasia: Evidence from eyetracking while listening. Brain and Language, 100: 1–22. doi: 10.1016/j.bandl.2006.06.004[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) found that divergences exist in IWAs' sentence-processing routines depending on whether they comprehended non-canonical sentences correctly or not, pointing rather to a processing deficit explanation.

Aims: The aim of the current study was to investigate agrammatic IWAs' online and offline sentence comprehension simultaneously in order to reveal what online sentence-processing strategies they rely on and how these differ from controls' processing routines. We further asked whether IWAs' offline chance performance for non-canonical sentences does indeed result from guessing.

Methods & Procedures: We used the visual-world paradigm and measured eye movements (as an index of online sentence processing) of controls (N?=?8) and individuals with aphasia (N?=?7) during a sentence–picture matching task. Additional offline measures were accuracy and reaction times.

Outcomes & Results: While the offline accuracy results corresponded to the pattern predicted by the TDH, IWAs' eye movements revealed systematic differences depending on the response accuracy.

Conclusions: These findings constitute evidence against attributing IWAs' chance performance for non-canonical structures to mere guessing. Instead, our results support processing deficit explanations and characterise the agrammatic parser as deterministic and inefficient: it is slowed down, affected by intermittent deficiencies in performing syntactic operations, and fails to compute reanalysis even when one is detected.     

Design,synthesis, evaluation,and molecular modeling studies of indolyl oxoacetamides as potential pancreatic lipase inhibitors

A series of indolyl oxoacetamide analogs was synthesized, characterized, and evaluated for their pancreatic lipase inhibitory activity using porcine pancreatic lipase (type II) and 4-nitrophenyl butyrate. Compound 8d exhibited a potent inhibition, with an IC₅₀ value of 4.53 µM, followed by 8c (IC₅₀ = 5.12 µM), compared with the standard drug, orlistat (IC₅₀ = 0.99 µM). Furthermore, analogs 8c and 8d exhibited a reversible competitive inhibition, similar to orlistat. Molecular docking studies of the compounds 7a–f and 8a – f were in agreement with the in vitro results, wherein 8d exhibited a potential MolDock score of −163.052 kcal/mol. A 10-ns molecular dynamics simulation of 8d complexed with pancreatic lipase confirmed the role of π–π stacking and π–cation interactions with the lid domain and Arg 256, respectively, in stabilizing the ligand at the active site (maximum observed root mean square deviation ≈ 2 Å). The present study led to the identification of novel indolyl oxoacetamides ( 8a – d ) as potential pancreatic lipase inhibitory leads that might further result in enhanced potency through lead optimization.     

Beta- and gamma-frequency coupling between olfactory and motor brain regions prior to skilled,olfactory-driven reaching

A major question in neuroscience concerns how widely separated brain regions coordinate their activity to produce unitary cognitive states or motor actions. To investigate this question, we employed multisite, multielectrode recording in rats to study how olfactory and motor circuits are coupled prior to the execution of an olfactory-driven, GO/NO-GO variant of a skilled, rapidly executed (∼350–600 ms) reaching task. During task performance, we recorded multi-single units and local field potentials (LFPs) simultaneously from the rats’ olfactory cortex (specifically, the posterior piriform cortex) and from cortical and subcortical motor sites (the caudal forepaw M1, and the magnocellular red nucleus, respectively). Analyses on multi-single units across areas revealed an increase in beta-frequency spiking (12–30 Hz) during a ∼100 ms window surrounding the Final Sniff of the GO cue before lifting the arm (the “Sniff-GO window”) that was seldom seen when animals sniffed the NO-GO cue. Also during the Sniff-GO window, LFPs displayed a striking increase in beta, low-gamma, and high-gamma energy (12–30, 30–50, and 50–100 Hz, respectively), and oscillations in the high gamma band appeared to be coherent across the recorded sites. These results indicate that transient, multispectral coherence across cortical and subcortical brain sites is part of the coordination process prior to sensory-guided movement initiation. Raymond Hermer-Vazquez, Linda Hermer-Vazquez these two authors contributed equally.     

N-hydroxy-pyrroline modification of verapamil exhibits antioxidant protection of the heart against ischemia/reperfusion-induced cardiac dysfunction without compromising its calcium antagonistic activity

Any clinical intervention (e.g., coronary angioplasty, thrombolysis) used to reintroduce blood flow to an ischemic region of the myocardium is accompanied by a complex enzymatic cascade of reactions resulting in severe injury to the heart, termed myocardial ischemia/reperfusion (I/R) injury. In this study, we evaluated the ability of H-3010 (1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid (2-(3,4-dimethoxyphenyl)-5-([2-(3,4-dimethoxyphenyl)ethyl]-methylamino)-2-isopropylpentyl)-amide), a pyrroline modification of verapamil (2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylmethyl-amino]-2-(1-methylethyl)pentanenitrile), to protect the heart against I/R-mediated injury. Isolated perfused rat hearts pretreated with verapamil and H-3010 were subjected to 30 min of global no-flow ischemia followed by 45 min of reperfusion. The recovery (expressed as a percentage of preischemic baseline) in contractile function (left ventricular developed pressure) of hearts subjected to I/R was significantly higher in hearts treated with H-3010 at 5 microM (51.0 +/- 6.4%) as well as at 50 microM (75.1 +/- 7.4%) as compared with verapamil at 5 microM (32.2 +/- 3.7%) or untreated control hearts (18.1 +/- 2.8%). Creatine kinase release was significantly attenuated in hearts treated with H-3010 (45.7 +/- 4.5 U/liter) as compared with untreated controls (131.5 +/- 6.4 U/liter). Similar trends were also observed for lactate dehydrogenase release as well. A marked reduction in percent area of infarction was observed in the H-3010 group (11.7 +/- 1.6%) compared with verapamil (25.1 +/- 2.9%) and control (41.3 +/- 1.9%) groups. Additional in vitro studies showed a marked decrease in reactive oxygen species generation with H-3010. In conclusion, our data clearly demonstrated that the verapamil derivative, H-3010, significantly decreased I/R-induced cardiac dysfunction. This can be attributed to the combined benefits of the pyrroline moiety (antioxidant) and the parent verapamil component (antiarrhythmic) in the protection of the heart from I/R-induced injury.     

Case report of a uniocular topography guided laser-assisted in situ keratomileusis enhancement following an incorrectly treated astigmatic axis

A 23-year-old male presented to us wanting spectacle removal for cosmetic purposes. He underwent bilateral wavefront optimized (WFO) laser-assisted in situ keratomileusis (LASIK) on the Alcon Wavelight^® EX-500 excimer laser with an incorrectly treated astigmatism axis for left eye due to a manual data entry error in the laser. WFO LASIK treats the sphere and cylinder only. LASIK enhancement with topographic-guided ablation resulted in the elimination of all refractive errors and gave excellent results. Wavelight^® topographic-guided treatment can perform two separate layers of correction in the same ablation: The first is to treat the corneal irregularities for the higher order aberration (HOA) removal, the second one meant to treat the sphere and cylinder if indicated.     

Synthesis and characterization of 2-(4-((1-alkyl or aryl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)naphtho[1,2-d]oxazoles for protein tyrosine phosphatase 1B inhibitory activity

2-(4-((1-Alkyl/aryl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)naphtho[1,2-d] were prepared and evaluated as protein tyrosine phosphatase 1B (PTP1B) inhibitors. In this study, two new compounds with potent PTP1B inhibitory activity were identified.